The human monocyte possesses two distinct receptors which mediate phagocytosis, the Fc receptors and the recognition unit for particulate activators of the human alternative complement pathway. The recognition unit is distinct from the Fc and C3b receptors by its trypsin sensitivity, its specificity for activators, its continued expression by cultured monocytes, and its being opsonin-independent. It, thus, constitutes a phagocytic system of natural immunity that is available to the nonimmune host. A humoral component, present in fibronectin preparations and in cryoprecipitates, has recently been demonstrated to augment markedly the ingestion of activators and to have absolutely no effect on Fc-mediated ingestion or C3b-adherence. This humoral component is a protein and mediates its specific augmentative effect by binding to the activators, rather than by activating the human monocytes. Preliminary studies suggest that this active component is an altered form of plasma fibronectin, which in its native form lacks phagocytosis-enhancing activity. The proposed research seeks to define the nature of this humoral component. Research will be directed first, at determining the best source material that exhibits maximum levels of activity, second, at isolating and purifying the active component to homogeneity, third, at determining the antigenic relatedness of the active component to plasma fibronectin with hybridoma antibodies, fourth, at isolating the active component from enzymic digests of native plasma fibronectin, fifth, at determining whether the activators after interaction with the active component acquire an enhanced capacity to activate the plasma proteins of the human alternative complement pathway, and finally, at determining with the hybridoma antibodies, whether fibronectin is associated with the human monocyte and participates in the ingestion of activators. That an adjunct, non-complement, humoral component, other than IgG, only augments a phagocytic system of natural immunity may represent an essential component for the normal physiologic function of host defense in vivo.